1. Field of the Invention
The present invention relates to a preparation for topical treatment of skin or eye diseases caused by viral infections.
2. Description of the Related Art
Treatment of viral diseases in humans is a major focus of medical science. While some progress has been made, viral infections are still among the diseases most difficult to treat. Despite growing understanding of viral diseases along with improved techniques for detecting and treating them, few antiviral drugs have proved effective. Some viral diseases such as HIV are life threatening; others such as herpes simplex virus and influenza virus continue to cause severe problems. Further, new viral diseases constantly appear as an inevitable consequence of evolution. Thus, searching for a novel and effective way of treating viral diseases remains imperative and challenging.
Product R1 emerged as an antiviral product in the 1930""s. While it was originally believed to be a product composed of peptone, peptides and nucleic acids (fully defined hereafter), the precise composition remains unidentified. Nevertheless, Product R has demonstrated an ability to inhibit rapidly the course of several viral diseases. It is nontoxic, miscible with tissue fluids and blood sera and free from anaphylactogenic properties.
1. The agent is known under the trademark xe2x80x9cReticulosesxe2x80x9d, a trademark of Advanced Viral Research Corp. 
Despite these early promising clinical reports, systematic studies have rarely been performed to establish clinical utility. Optimum dosages of Product R for treating viral infections as indicated above have been poorly investigated. In fact, most of the clinical reports lacked necessary controls and statistically sufficient samples for evaluating the effectiveness of Product R. Note, two earlier publications challenged that Product R failed to demonstrated antiviral activity. In light of this background, the present status of the art of using Product R in treating viral infections remains questionable. Close examination of the development history of Product R reveals no meaningful pattern that could be followed to designate a treatment for a particular viral infection, for viruses causing those infections are extremely diversified in their genetic traits or/and pathogenesis. In addition, earlier clinical applications described Product R only as an agent to be administered alone. Product R has never been suggested to be applied in combination with other antiviral drugs; nor has Product R been administered for a period longer than about two months. Given the limits of prior art, developing new treatment strategies using Product R is desirable.
In developing an antiviral agent, it is well known that inhibitory activity of an antiviral agent against a particular virus cannot be equated with its inhibitory effect against another virus. For example, acyclovir has proved to be specifically effective against herpes simplex 1 and 2 (HSV 1 and 2) but not against cytomegalovirus (CM), even though both HSV and CM belong to the same herpesvirus family, sharing certain genetic features. The specificity of acyclovir rests on the activity of the thymidine kinase gene unique to HSV 1 and 2, indicating that a distinctive feature of each individual virus forms a basis for developing an antiviral agent specifically against this very virus. In other words, treatment of a viral infection using a certain antiviral agent does not necessarily indicate that the same agent will produce the same effect when used for treating other viral infections. The genetic diversity of viruses further mandates that an attempt to be made to discern the effectiveness of a new application of an antiviral agent to a different virus.
An antiviral agent usually interacts with molecules involved in different stages of viral infections: in early events such as adsorption, penetration (internalization), and uncoating; in virus replication characteristic for each virus genome and components of the nucleoprotein complex; and in the chemistry of metabolic pathways. The best targets for inhibition by an antiviral agent are molecules serving a function unique to the virus, with no analogous counterpart in host cells. In order to identify the virus-specific molecule with which a putative antiviral agent interacts, it is important to characterize viruses in terms of particle and genome structure, as well as to define specific biochemical events that occur in infected cells. Although progress has been made in discovering molecules necessary for virus adsorption, replication and metabolism, current knowledge remains insufficient to explain many aspects of these events. Consequently, not every antiviral agent""s function is fully defined in terms of its interaction with a target virus through one or a series of the indicated events; much less is understood where an antiviral agent is employed to treat a new viral infection, especially if the antiviral agent has been poorly characterized. Without the knowledge of a virus"" genetic traits and the chemical properties of an antiviral agent, treatment of a viral infection becomes unpredictable.
HSV, is known to cause fever blisters and cold sores, among the most prevalent viral infection. There are two HSV strains. Type-1 strain commonly causes herpes labialis located on a lip, and keratitis, an inflammation of the cornea. Type-2 is usually located on or around genital area and is generally transmitted primarily by direct contact with herpetic sores or lesions. Generally, HSV 1 occurs above the waist and HSV 2 occurs below the waist.
Estimated frequency and location of oral (HSV 1) and genital (HSV 2) infections are about half million of primary cases of type-1 per year, with 98 million of recurrent cases per year in the United States alone. Of the genital type-2 cases, there are around 500,000 cases of primary genital herpes with 3-9 million of recurrent cases per year in the United States.
HSV infection is a recurrent infection characterized by the appearance on the skin or mucous membranes of single or multiple clusters of small vesicles, filled with clear fluid on slightly raised inflammatory bases. These symptoms usually accompany a flu or some such other state where the body resistance is low. HSV is very infectious and it is rapidly and easily transferable by contact.
Herpetic lesions may appear anywhere on the skin or mucosa, but are more frequent about the mouth, on the lips, on the conjunctiva and cornea, and on or around the genitalia. Following a short prodromal period of tingling discomfort or itching, small tense vesicles appear on the erythematous base. Single clusters vary in size from 0.1 to 1.5 cm. The vesicles persist for a few days, then begin to dry, forming a thin yellowish crust. Healing is long and usually begins 7-10 days after onset of the viral infection and is complete by about 21 days. Healing may be slower, with secondary inflammation, in moist body areas. Individual herpetic lesions usually heal completely but recurrent lesions at the same site may cause atrophy and scarring. It will be appreciated that the herpes simplex outside or inside mouth, lips, cheeks, chin and particularly on or around the genitalia is very painful and uncomfortable as it burns or itches, as well as ungainly, with an often open sore on the lip and, particularly as it does on recurrence, leaving the ugly lesions on or around lips.
The HSV 2 has even greater and more severe, if possible, consequences. Due to its location on or around the genital area, a social stigma attaches to this type of herpes infection which is categorized as a venereal disease. The viral disease itself is much the same as the HSV 1. Initial and recurring attacks, similar but probably more severe than those of type-1, occur in the neighborhood of the genital organs. The initial attack begins with swelling, reddening, and pain in the area surrounding the site of infection with the inflammation developing and extending over the whole groin, thighs and buttocks. This is accompanied by a low-grade fever, mild flu-like symptoms and swelling of the lymph glands in the groin. The development of small, blister like sores soon follows over much of inflamed area rapidly becoming grayish yellow and ulcerous. These blisters typically last for about two weeks. The symptoms in recurrent episodes are generally not so severe but nonetheless unpleasant and uncomfortable. The recurrence may occur as often as several times a month.
Treatment of genital herpes is primarily by systemic administration of antiviral drugs as described above, for example by IDU and trifluridine (TFT) with all dangers connected with their high cytotoxicity, with ARA-A, another antiviral with somewhat less toxicity, and acyclovir or bromovinyldeoxyuridine which are both enzyme inhibitors semi-specific to virus replication. All these agents are given primarily systemically and have high probability to cause severe side effects, as discussed above. Moreover, none of these agents is a selective inhibitor of only the herpes simplex virus replication but they effect also a replication of normal cells. Therefore, when used in doses large enough to seek and destroy all the active herpes viruses dormant in the sensory ganglia, these compounds may also be highly disruptive to the normal DNA in the host cells in which the virus multiplies. This is a highly undesirable result since the replication of normal cells is also effected. The topically administered acyclovir ointment seems to be effective in the treatment of primary first occurrence of genital herpes infection but has little if any, effect on recurrent genital herpes disease.
Thus, it would be advantageous to have available treatment of genital herpes which would prevent development of painful sores and inflammation in the genital area, prevent their recurrence and yet be innocuous enough toxicologically so that no systemic administration of cytoxic chemical substances is necessary or needed.
Another form of viral herpes disease is so called herpes zoster, commonly known as shingles. Herpes zoster is a disease of middle or old age characterized by extreme pain in a limited area of the upper body or face and an outbreak of small pimply blisters in the same area usually along the nerve branches. The herpes zoster is caused by varicella-zoster virus, the same virus that causes chickenpox. Herpes zoster is an acute central nervous system infection involving primarily the dorsal root ganglia and characterized by vesicular eruption and neuralgic pain in the cutaneous areas supplied by peripheral sensory nerves arising in the affected root ganglia in which the inflammatory changes occur.
There is no specific therapy for this extremely painful viral infection. Corticosteroids, if given early, may relieve pain in severe cases. Aspirin and other anti-inflammatories or antiviral agents systemically may alleviate the pain. However, these agents have undesirable side effects.
Thus, it would be extremely important to find an agent which would alleviate the pain connected with the symptomatically occurring blisters during herpes zoster attack.
Another viral infection which may severely effect the patient in that it disfigures patient""s face is varicella also know as chickenpox caused by varicella virus. This is a rare form of chickenpox in which the eruption leads to a gangrenous ulceration. There is severe scarring (pock marking) following the healing of the ulceration which never disappears and the person""s face is forever disfigured. Moreover, there is no treatment known or prevention for the chickenpox or the subsequent scarring.
Consequently, it would be desirable to have available treatment and/or prevention for the gangrenous ulceration before it results in the scars.
Another highly unpleasant and painful conditions are genital warts caused by human papillomavirus (HPV). Not only this condition is unpleasant and painful but it may also contribute to cervical and genital cancers.
Thus, it would be advantageous and highly desirable to provide an effective treatment against genital warts.
An object of this invention is to provide a preparation that is effective in topical treatment of infections caused by viruses including HSV 1 and 2, herpes zoster, genital warts chickenpox and adenovirus, etc. This has been accomplished by using Product R alone or in a pharmaceutical composition containing Product R.
One aspect of the present invention relates to a method for treating patients having skin diseases caused by viral infections by administering Product R topically to the area of the infections, using Product R alone or in a pharmaceutical composition containing Product R.
Another aspect of the present invention relates to a method for treating patients having eye afflictions caused by viral infections by administering Product R to the patients"" eyes, using Product R alone or Product R with pharmaceutical acceptable carriers.
Still another aspect of this invention relates to a pharmaceutical composition for topical treatment containing an effective treatment amount, i.e. at least 50% by weight, of Product R.
Other objects and features of the present invention will become apparent from the following detailed description considered in conjunction with the accompanying drawings. It is to be understood, however, that the drawings are designed solely for purposes of illustration and not as a definition of the limits of the invention, for which reference should be made to the appended claims.